ArticleOrganic & biomolecular chemistry2014
Next generation maleimides enable the controlled assembly of antibody-drug conjugates via native disulfide bond bridging.
Article in Organic & biomolecular chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed.
- Site-Specific Labeling of PD-L1 Fab through Disulfide Rebridging for ImmunoPET Imaging.Chemical & biomedical imaging · 2026Article
- On-resin assembly of cysteine-reactive linkers for controlled site-selective antibody bioconjugation.Nature protocols · 2026Review
- Enabling the synthesis of multi-payload thio-antibody conjugates through the use of pyridazinediones,RSC chemical biology · 2026Article
- Antibody-Antibiotic Conjugates: Mechanisms, Clinical Progress, and Next-Generation Strategies Against Multidrug-Resistant Bacterial Infections.MicrobiologyOpen · 2026Review
- A Modular and Convergent "Stick and Click" Conjugation Platform Enables Fast Antibody Conjugate Library Synthesis.Bioconjugate chemistry · 2026Article
- Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies.Beilstein journal of organic chemistry · 2026Review
- Achieving cysteine-selective peptide/protein bioconjugation via tunable triazine-pyridine chemistry.Science advances · 2025Article
- Mass spectrometric imaging and quantitative analysis of theInorganic chemistry frontiers · 2025Article
- Unsaturated Phosphine Oxides for Modular Antibody Rebridging and Single Reagent Peptide-Cyclization-Bioconjugation.Angewandte Chemie (International ed. in English) · 2025Article
- Unleashing the Antiviral Potential of Stapled Peptides: A New Frontier in Combating Human Neurotropic Viral Infections.Microbial biotechnology · 2025Review
- Antibody-Drug Conjugates: A Start of a New Era in Gynecological Cancers.Current oncology (Toronto, Ont.) · 2024Review
- Site-Selective Antibody Conjugation with Dibromopyrazines.Bioconjugate chemistry · 2024Article
- Chemo- and regio-selective differential modification of native cysteines on an antibodyChemical science · 2024Article
- Homogeneous multi-payload antibody-drug conjugates.Nature chemistry · 2024Review
- Exploring the next generation of antibody-drug conjugates.Nature reviews. Clinical oncology · 2024Review
- Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice.Experimental hematology & oncology · 2024Review
- The Nitrile Bis-Thiol Bioconjugation Reaction.Journal of the American Chemical Society · 2024Article
- Use of pyridazinediones for tuneable and reversible covalent cysteine modification applied to peptides, proteins and hydrogels.Chemical science · 2023Article
- Two Birds with One Stone: A Novel Dithiomaleimide-Based GalNAc-siRNA Conjugate Enabling Good siRNA Delivery and Traceability.Molecules (Basel, Switzerland) · 2023Article
- Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E-based Antibody-Drug Conjugate for Treatment of Nectin-4-expressing Cancers.Molecular cancer therapeutics · 2023Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
The advent of Adcetris™ and Kadcyla™, two recently FDA-approved antibody-drug conjugates (ADCs), in the clinic has had a major impact on the treatment of lymphoma and breast cancer patients, respectively, worldwide. Despite these successes many new ADCs fail at various stages of development, often due to shortcomings in the methods used for their assembly. To address this problem we have developed next generation maleimides (NGMs), which specifically re-bridge reduced interchain disulfide bonds and allow the efficient conjugation of small molecules to antibodies, without the need for engineering of the target antibody. The method is site-specific and generates near homogeneous products in good yields. Moreover, adjustment of the reaction conditions allows control of the conjugation in terms of stoichiometry (drug-loading) and site selectivity. Using this method we prepared a series of ADCs from trastuzumab and doxorubicin (DOX) with a controlled drug-to-antibody ratio (DAR) of 1, 2, 3 and 4. All of these constructs were fully active by ELISA and had more than 90% of re-bridged disulfide bonds by CE-SDS when compared to clinical grade antibody. Furthermore, digest experiments of the DAR 2 material revealed that almost all of the drug had been targeted to the Fab arms of the antibody. Thus, NGMs offer a flexible and simple platform for the controlled assembly of ADCs from an antibody.
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